Diarylprolinol‐Mediated Asymmetric Direct Cross‐Aldol Reaction of α,β‐Unsaturated Aldehyde as an Electrophilic Aldehyde

Abstract

The diarylprolinol‐mediated asymmetric direct cross‐aldol reaction of α,β‐unsaturated aldehyde as an electrophilic aldehyde was developed. The reaction becomes accelerated by an acid when a carbonyl group is introduced at the γ‐position of the α,β‐unsaturated aldehyde. Synthetically useful γ,δ‐unsaturated β‐hydroxy aldehydes were obtained with high anti‐selectivity and excellent enantioselectivity.

Efficient Catalytic Methods for Asymmetric Cross‐Aldol Reaction of Aldehydes

“…Although simple α,β-unsaturated aldehydes such as cinnamaldehyde did not participate as an acceptor in the diarylprolinol 54 catalyzed aldol reaction with donor alkyl aldehydes, the γ-oxo-α,β-unsaturated aldehydes were found to be suitable electrophilic partners. [80] They reacted with nucleophilic aldehydes in the presence of catalyst 54 and acetic acid to yield the aldol products with high diastereoselectivity favouring the antiproduct and also with high enantioselectivity (Scheme 29). Acetic acid probably protonated the γ-carbonyl group in the unsaturated acceptor aldehyde and thus increased its reactivity.…”

Three-Pot Synthesis of Chiral Anti-1,3-diols through Asymmetric Organocatalytic Aldol and Wittig Reactions Followed by Epoxidation and Reductive Opening of the Epoxide

“…We developed diarylprolinol 1 , substituted with trifluoromethyl groups, as an effective organocatalyst for the asymmetric cross-aldol reaction of two different aldehydes . The β-hydroxy aldehydes, which are generated with excellent enantioselectivity, are useful chiral building blocks.…”

“…In the second epoxidation reaction, only anti -γ-alkyl-δ-hydroxy α,β-unsaturated carbonyls reacted to afford epoxides, with recovery of syn -γ-alkyl-δ-hydroxy α,β-unsaturated carbonyls, which were easily separated. Given that the first cross-aldol reaction proceeds with excellent enantioselectivity with a wide variety of substrates, the final 1,3-diols were obtained with excellent enantioselectivity. Given that we previously reported the synthesis of β,δ- syn -dihydroxy carbonyls based on an asymmetric cross-aldol reaction as one of the key steps (eq ), both anti - and syn -β,δ-dihydroxy carbonyl units can be prepared by using the same aldol reaction.…”